The developmental biology studies the processes by which individual organisms grow and from a single cell to a complex multicellular organism development ( ontogeny ). Developmental biology has its origins in embryology and today deals with genetic and epigenetic processes of the self-organization of cells on the basis of inherited gene regulation networks , the physico-chemical properties of cells and tissues, and environmental factors.
The term developmental genetics is used largely synonymously, but it can also refer to aspects of behavioral genetics , but neglects epigenetic aspects of development. Developmental neurobiology studies the maturation of the nervous system . Evolutionary Developmental Biology (EvoDevo) deals with the connections between developmental biology and evolution .
Development of animals
Ernst Haeckel defined development as the entire process from the fertilized egg cell to the adult organism. Today we see development as a genetic and epigenetic process of the self-organization of cells on the basis of inherited genetic networks, the physico-chemical properties of cells and tissues as well as environmental factors.
Factors, mechanisms and main stages of development
The development proceeds as a complex interplay of various genetically determined development factors (gene products) such as B. morphogens , adhesion molecules , growth factors , development genes, but also epigenetic development factors such as chromatin changes and factors of the internal and external environment of the embryo and secondly of development mechanisms such. B. induction , cell proliferation , cell differentiation , cell migration , signal transduction , apoptosis , cell growth or pattern formation .
Genetically determined development factors include a number of genes or gene products ( proteins ) that are effective in development . A morphogen is a substance that controls the spatial order of cell differentiation and thus indirectly the formation of form. Morphogens can thus cause pattern formation during morphogenesis . Adhesion molecules are proteins that cause adhesion to a cell or to a substrate (e.g. cadherins , integrins ). A growth factor is a protein that must be present in the extracellular space in order for certain cell types to grow and develop normally. These include, for example, bone morphogenetic proteins . Developmental genes come in classes. A distinction is made between maternal effect genes for determining the polarity of the embryo, segmentation genes for the segmental structure of the embryo, compartment genes for field subdivisions, history regulation genes for cellular differentiation and, as one of the most important classes, homeotic genes for determining the identity of segments and field genes for determining the organ - Plant fields (e.g. eyeless). Mutations within homeotic genes can lead to the transformation or loss of organ structures or parts of the body. As a characteristic sequence, these genes always contain a homeobox which codes for a transcription factor . The best known homeotic genes are the Hox genes .
Epigenetic factors are influences that cause epigenetic changes in cells. A distinction is made between epigenetic factors of the internal and external environment. The internal environment includes the chemical composition of the internal environment of the embryo, in particular the surrounding cells and interactions between cells and cell populations, but also the spatial-geometric conditions of growing tissues and organs. The external environment includes the chemical composition of the environment, nutrition, and physical conditions such as light, mechanics, gravity (egg polarization) and temperature ( sex determination in turtles and crocodiles).
The term epigenesis describes the gradual processes of embryonic morphogenesis of organs . These are based on mechanisms at the level of cells and cell associations, these are Turing mechanisms or general pattern formation processes in biology. Examples of this can be found in the explanation of the embryonic extremity development in vertebrates.
A number of specific developmental mechanisms, the developmental physiology, determine the specific course of morphogenesis : Induction is the influence on the development of one embryonic target group by another, which releases induction substances, e.g. B. the induction of lens development in the vertebrate eye by ectodermal tissue. Cell proliferation is repeated, rapid, and controlled cell divisions that lead to tissue growth. Cell differentiation means on the one hand the differentiation of cells in comparison with one another, on the other hand the individual cell development and thus the differentiation of a cell in the course of development time. The determination, that is, the programming of a cell, takes place on a certain development path. A programmed but not yet fully differentiated cell is given the designation "-blast" , the mature, fully differentiated cell is called "-cyt". A distinction is made between the reversible specification of a cell and its non-reversible differentiation or determination or commitment. Cell differentiation, together with cell division (mitosis), is a necessary but not sufficient requirement for a developing, multicellular embryo to maintain its shape (morphogenesis). In molecular biology, cell differentiation is expressed in the fact that not the entire genome is used simultaneously for protein production, but only the genes relevant for the respective cell type are active. One speaks of differential gene expression.
Stem cells are cells that have retained their ability to divide and only differentiate further after they have multiplied. After the asymmetrical division, one daughter cell remains a stem cell, the other takes a new path. Stem cells are differentiated according to their development potential: Totipotent stem cells ( egg cells ) can produce the entire organism. Pluripotent stem cells are embryonic stem cells from the blastoderm that have not yet been assigned to a specific cell type. They produce cells of various types that can belong to any of the cotyledons. Multipotent stem cells can produce different cells from a particular lineage; H. various derivatives of a cotyledon. Unipotent stem cells differentiate into a single cell type, e.g. B. Stem cells of the epidermis of the skin. With the progress of development, there is an increasing limitation of the development potential of cells from totipotent to pluripotent and multipotent to unipotent. Under cell migration is defined as the change of location of active cells or cell aggregates, for example in the development of the nervous system. Signal transduction describes the chain of events for transmitting a message from the outside of the cell across the cell membrane into the inside of the cell. Signal transduction starts when an extreme signal molecule, a ligand, binds to membrane-anchored receptor molecules. Apoptosis is the controlled, programmed cell death without affecting the surrounding tissue and affects tissue that is only required in a certain development phase and is then broken down into vesicles and destroyed by macrophages , e.g. B. the mesenchymal spaces between fingers and toes in vertebrate extremities or the loss of the tail of the tadpole.
Self-organization as a development principle means the emergence of order from initial disorder or structuring from non-structuring of cells and tissues. Here, an initial, possibly small change in a parameter such as a gene activity can often cause a non-linear, non-chaotic reaction of the entire system via threshold effects. Finally, processes of pattern formation create well-ordered and reproducible spatial patterns of differentiated cells. This can be two-dimensional, for example in the formation of color patterns on skin (fish) and fur (zebra, cheetah), butterfly wings or bird plumage (circles, rhombuses, stripes), and three-dimensional, for example in vertebrate extremity development or in training neural pattern. The theoretical basis for pattern formation is the Turing model or Turing mechanism , a chemical reaction-diffusion model in which Turing first described the chemical basis of morphogenesis in 1952. The Turing model was expanded to a model with local activator and lateral inhibition (LALI model). LALI models detach themselves from chemical reactions and allow patterning at cell level through cell interaction. Pattern formation processes are therefore not genetically determined in detail. In addition to genetically necessary conditions, there is sufficient information about the actual pattern formation processes at the cell level and is therefore epigenetic.
In the course of development, differentiated cells for specific tissue types (skin, muscles, nerves, organs, etc.) are formed. There are regions of the embryo in which one or a few very specific genes of the cells are expressed and certain signal proteins are produced in a very specific phase of development. The ability to activate differently conserved core processes in different places at certain times in the organism and to create these reaction spaces is called compartmentalization . An insect embryo forms approx. 200 compartments in the middle phase of development. The expression of these compartments is the actual task of the Hox genes.
Stages of development
The main stages of development are in chronological order zygote → cleavage → gastrulation → organogenesis → fetogenesis → larval stage ( larval development with metamorphosis ) → juvenile stage (growth) → adult stage → (maturity), aging → death . The phases zygote, furrowing and gastrulation are referred to as early development.
Selected stages of embryonic mouse development (E = Embryonic day)
|E2.0||First furrow after 24 hours. Holoblastic groove . Cell cycle 12 hours, relatively long compared to Xenopus. 4-16 cells|
|E3.5||Embryo. Blastocyst consists of trophoblast (nutritional part), internal cell mass and blastocoel|
|E4.0||Epiblast and primitive endoderm. Embryoblast and aembryonic pole recognizable. aembryonic pole = mainly epiblast , embryonic pole = blastocoel|
|E4.5||Implantation of the blastocyst in the lining of the uterus .|
|E5.0||First signals to establish the antero-posterior axis of the body.|
|E5.5||Invagination (invagination) of the prospective endoderm into the inner, fluid-filled cavity (blastocoel) of the blastula. Inner part = endoderm, outer part = ecoderm. Narrowing of the blastula. Invagination = primitive gut (archenteron); Opening = original mouth (later anus)|
|E6.0||Extraembryonic ectoderm in the invagination. Proamnium cavity = secondary body cavity|
|E6.5||Cylindrical structure of the embryo. Onset of gastrulation|
|E7.5||Neural plate. Onset of neurulation. Heart tube|
|E8.0||First 8 pairs of somites. Ear placode|
|E9.0||Primordial germ cell migration. 16 pairs of somites. Anterior extremity buds. Back bud about half a day later.|
|E10.0||Lens vesicles separated in the eye.|
|E11.0||Extremity development . Earliest signs of toes. 45-47 pairs of somites|
|E11.5||Eye boundaries clearly visible. Front limb bud forms hand plate|
|E13.0||53-55 pairs of somites. Hair follicles over the eyes and ears. Elbow. Wrist bones. Auditory ossicles.|
|E14.0||56-60 pairs of somites. Palate. Cap stage of the teeth|
|E15.0||Inner ear: the cochlea ( cochlear ). Gonads. Apoptosis of the spaces between the toes. Pancreas. Lung. Bell stage of the teeth|
|E15.5||Olfactory development (sense of smell)|
|E16.0||Forebrain, brain restructuring|
|E17.0||Skin thickening and folds, long whiskers|
|E18.0||Eyes faintly visible through eyelids|
History of science in embryology
Development of important animal model organisms
The development is described using model organisms. Model organisms have to meet a number of requirements, including extensive breeding, short generation times, simple and inexpensive keeping, the presence of natural mutants, inducible oviposition, a high number of offspring and simple observation and investigation methods. The zebrafish ( Danio rerio ), the smooth clawed frog ( Xenopus laevis ), the chicken ( Gallus gallus ) and the house mouse ( Mus musculus ) serve as model organisms of the developmental biology of vertebrates . In invertebrates, the sea urchin germ is used as a reference model for fertilization and early development . In addition, the fruit fly Drosophila melanogaster , the nematode Caenorhabditis elegans or Pristionchus pacificus , the flour beetle Tribolium castaneum and the crab Partiale hawaiensis are used as model organisms for development studies.
Vertebrate embryonic development
As a result of meiotic cell division, the germ cells (gametes) form the haploid cells, which are used for sexual reproduction and grow in the respective parental organism as a female egg cell (oocyte) and male sperm . The haploidy of the gametes is the prerequisite for the genetic recombination during fertilization and thus for the genetic diversity in the population.
Fertilization or fertilization is the fusion of male and female germ cells. Parental genetic material is mixed up in the course of sexual reproduction. This is the actual complex process of initiation of embryonic development. The sperm and egg cell attract each other with the help of diffusible substances that are released by the egg cell and have a chemoattractive effect on the sperm. In addition, a sperm succeeds in docking with the egg cell. The membranes of both germ cells fuse. The male pronucleus penetrates the egg cell. There is a change in the membrane potential of the egg cell, which prevents further sperm from entering ( polyspermia ). After the sperm has penetrated the nucleus of the egg cell, the egg cell is fertilized by the fusion of the two cell nuclei and now has the hereditary material of the father and mother as a zygote .
After fertilization, embryogenesis begins with cleavage as the first phase. The furrow is the rapid succession of repeated cell divisions by constricting the zygote. The process runs synchronously for all cells. After 7 days and 7 rounds of cleavage, the human germ consists of a little over 100 cells, about ten of which are embryoblast cells .
The purpose of the cleavage is rapid cell division at the beginning of development, starting from the zygote. The resulting cell association remains the same size, because additional cell plasma material is not provided. A distinction is made between different types of grooves according to the geometry of the individual pitches . The stages of furrowing lead to the formation of the morula , a sphere filled with cells. Then the development of the blastula begins , or in mammals the blastocyst , a fluid-filled hollow sphere. The resulting cavity inside, the blastocoel , is the primary body cavity. The blastula is divided into five territories after six cell division cycles, which in the frog Xenopus laevis already contain all three cotyledons.
In the mammals, evolutionary structures appear in the early phase that distinguish them from the aquatic amphibians. The amniotic cavity is created in the inner cell mass of the blastocyst , which protects the embryo of all amniotic animals and allows it to develop independently of a habitat in external water ( amniotic fluid ). In fish, reptiles and birds, a yolk sac is formed, an extraembryonic, membranous structure that nourishes the embryo. In mammals this is only temporarily present in a reduced form. Because the blastocyst of a mammal differentiates itself after the cleavage into trophoblast , an extraembryonic cell layer that provides the nourishing connection to the uterus, and embryoblast . The actual embryo emerges from the embryoblast. In contrast to this, in amphibians the entire blastula becomes a larva , so they do not develop any embryonic covering tissue.
The embryonic cells of the embryoblasts of a mammalian germ are still pluripotent and show no discernible differences from one another, but they now stand out from the trophoblast cells. Totipotent cells are only present in the earlier stages, in humans possibly still in the eight-cell stage.
Gastrulation and cotyledonous formation
Gastrulation leads in alternative ways to the invagination of the blastula at its vegetative pole and to cell displacements in the interior of the blastula. The blastula is reorganized in the course of gastrulation. With the new mouths (deuterostomia), to which the vertebrates belong, the point of invagination is the original mouth, which becomes the anus, while at the opposite pole the mouth breaks through again (new mouth), which ends the gastrulation. The gesticulation creates a multi-layered organization that has three cotyledons in bilaterally built animals ( bilateria ) and two cotyledons in diploblastic animals such as cnidarians and cortex jellyfish . Organ formation (organogenesis) begins from this basic organization. A distinction is made between endoderm , mesoderm and ectoderm . Cotyledons are the first embryonic cell layers from which not just one but several tissues and organs emerge. The digestive tract, pancreas, liver, respiratory tract, thyroid and urinary tract are formed from the endoderm. The mesoderm leads to the development of the subcutaneous tissue, notochord, cartilage, bones, skeletal muscles and blood cells. The ectoderm is mainly responsible for the development of the kidneys, skin and nervous system. However, the organs that are finally formed usually each have components of all three cotyledons. The mesoderm forms two additional layers, one layer sealing the inside of the body cavity and the other forming the outside of the intestine. Further mesoderm compartments each form cell suppliers for new organ sections.
Definition of the body axes
The decision as to where the front and rear ends, where the top and bottom, right and left are to be placed in the embryo ( body axes ) is one of the fundamental early developmental determinations and in some animals is already determined maternally in the egg cell. In principle, there are different mechanisms for determining the axes: External orientation aids can be gravity or light, for example with chickens, in which the head-to-tail polarity (cranial-caudal axis) is determined by gravity and by the direction in which the egg is Transport through the fallopian tube is set in rotation, while the back-abdominal polarity (dorso-ventral axis) lies in the structure of the egg itself. In Xenopus there is an animal-vegetative egg polarity. The entry point of the sperm causes a symmetry movement in connection with gravity. The tail pole then arises diagonally to the entry point of the sperm. In D. melanogaster, maternal determinants determine the antero-posterior axis largely via cytoplasmic determinants ( mRNA ) in the egg itself before fertilization . The bilateral symmetry here is largely under the control of the maternal genome. In the zebrafish, the animal-vegetative axis is oriented horizontally because of the horizontal position of the egg. The egg of the mouse is little preprogrammed in terms of axis formation. The polarity of the mammals has obviously not yet been determined even after the cleavage, although studies suggest that the point of entry of the sperm also plays a role here.
Organogenesis is the process in multicellular animal organisms in which the development of the organ systems takes place in the course of embryogenesis . Organogenesis follows cleavage and gastrulation; it is followed by fetogenesis .
Development of the nervous system
Development of the neural crest cells, descendants
Blood vessel development, heart development
Development of the genitourinary system
Development of the skull and face
Multicellular organisms have bisexual potency. The sex determination is done genetically via selector genes. These can be on the male chromosome (Y), as in humans (sex determining region between the SRY gene ), or on the female chromosome (X or W) as in the fruit fly. The unequal sex-determining chromosome is called the heterosome compared to the similar autosomes . Genotypic sex determination does not take place in animals according to a uniform principle. Some animals develop hermaphrodites , such as C. elegans . He also develops male, but not female, individuals. The annelids Ophryotrocha puerilis first develop a male phenotype and later a female one. If two females meet, the weaker of the two must develop back into a male in a duel. If two males meet, only one of the two will develop into a female. Crocodiles and many turtles develop sex modifyingly or phenotypically or epigenetically depending on the ambient temperature in the nesting nest. If the increasing gross temperature reaches a threshold , the sex changes from female to male.
Regeneration is the ability of an individual to recreate lost body parts throughout their life. Sponges , freshwater polyps (hydra) and strudelworms have a high regenerative capacity . Hydra can completely replace the head and foot, depending on where you cut them. It can also replace nerve cells. Among the amphibians, the tail amphibians (Urodela) can regenerate extremities as long as molting is still imminent. In addition to the one-off regeneration of the milk teeth in mammals, vertebrates can only break down striated syncytial muscle cells again into mononuclear cells, which then have the character of multipotent stem cells for the muscle tissue. The two problems with regeneration are identifying the type and size of the missing material and where the material for the replacement comes from. The first question is poorly clarified; the second involves either the use of multipotent stem cells or the transdifferentiation of cells, in which these are reembryonalized, i.e. dedifferentiated into an earlier state. The limited ability of most species to regenerate is seen as the main cause of compulsory death. Among the animals, only the hydra is considered to be potentially immortal due to its high regenerative capacity.
Control of cell growth and cancer
Cell proliferation is subject to strict growth control of cell number throughout development. For this, there are inhibiting factors in cells that diffuse in the intercellular diffusion space ( interstitium ). Differentiation factors, for example in cells (blasts) capable of replication, can promote cell growth in low concentrations, but trigger terminal differentiation in high concentrations. Growth-inhibiting substances often occur as cell adhesion molecules and as components of the extracellular matrix, also in non-diffusing form.
The common denominator of different types of cancer is the excessive, uncontrolled growth of certain cell types. Cancer overrides the cell-immanent or social control of proliferation or differentiation. Either the progenitor cells multiply too quickly without a sufficient number of differentiated cells, or growth is impaired without accelerating the cell cycle. In the more frequent second case, either the stem cell character of both daughter cells is retained during cell division, the division activity continues although the differentiation program has been completed, or cells are not eliminated or not eliminated in time by apoptosis.
Postnatal vertebrate development
Postnatal development in invertebrates
Metamorphosis means the abandonment of a first larval phenotype and the simultaneous development of a new phenotype. This occupies a new ecological niche and colonizes a new living space. Metamorphosis causes transformation on every organismic level. This ranges from the external morphology to the physiology to the new enzyme equipment of the cells. All manifestations of an organism that goes through one or more metamorphoses from the embryonic stage, through the larva , pupa to the imago , can be derived from the same genome. From the order of the base pairs of the DNA it is not possible to read in what form the phenotypes appear with today's knowledge.
To the development of the fruit fly
D. melanogaster is one of the oldest, best-studied model organisms in biology. Already at the beginning of the 20th century it was possible to localize genes in D. melanogaster on certain chromosomes as well as gene spacings on these, without molecular-biological genetic knowledge being available at the time. Among other things, basic knowledge of axis formation and body segmentation could be gained from the fruit fly. Morphogens are decisive for both processes, diffusing substances that develop concentration gradients of different strength and direction in the syncytial embryo. These gradients are already effective maternally in the oocyte before fertilization. They influence the transcription of other genes. In the course of a hierarchical cascade of gene activation, increasingly complex molecular pre-patterns, periodic patterns, which lead to synchronous zone formation and thus to the segmentation of the larval body. The relevant gene classes of segmentation genes for this are Mater Algene , gap genes , pair rule genes and segment polarity genes .
The study of the development of D. melanogaster led, among other things, to the discovery of the Hox gene complex. Mutations in the expression sequence of homeotic genes, including Hox genes, so-called homeotic mutations, led to the discovery of the Antennapedia mutant in Drosophila , an animal with legs instead of antennae growing out of its head. The Hedgehog signaling pathway and the master control gene Pax-6 , which plays a key role in initiating early eye development in vertebrates and invertebrates, were also described for the first time in D. melanogaster .
In contrast to the nematode, the overall development of D. melanogaster is to a large extent a regulatory development, since the programming of the various developmental paths is based on mutual agreement between cells, i.e. H. based on cell interactions. The development of individual cell types depends on their neighborhood.
On the development of the roundworm
As a model organism of invertebrates, the nematode Caenorhabditis elegans created insights into fundamental developmental processes. Some of the findings also apply to vertebrates. In contrast to vertebrate development, its development is characterized as strictly deterministic by cell constancy (eutelia). According to this, every adult hermaphrodite individual has exactly the same number of 959 cells. The cell divisions are asymmetrical in the early stages; all divisions up to the adult animal are analyzed individually and make it possible to create a cell tree for all adult cells and to precisely determine their respective development path. The mechanism of apoptosis was discovered in C. elegans , which leads to the fact that exactly 131 cells required during development are specifically degraded again without damaging neighboring tissues. Asymmetrical cell division, which leads to a larger and a smaller daughter cell, is responsible for the early development of the antero-posterior body axis. In contrast, direct cell-cell contacts are decisive for the dorso-ventral axis formation. The notch signal path is an important signal path in the latter . The Wnt signaling pathway also plays an important role in the early course of development . In contrast, signal pathways that generate diffusion and, as a morphogen, form a gradient, play no role in this animal. The overall development of the roundworm is a mosaic development , since the mosaic of determinants in the egg leads to an early assignment of tasks and allows the cells to follow their development path independently of others.
Development of plants
Development of important model organisms in plants
In plants, the small bladder cap moss ( Physcomitrella patens ), the thale cress ( Arabidopsis thaliana ), the maize ( Zea mays subsp. Mays ), the snapdragon ( Antirrhinum majus ) and the garden petunia ( Petunia hybrida ) are important model organisms.
Growth and development of plants
Methods of Developmental Biology
Developmental biology makes use of various methods, most of which are also known from genetics. The most important are:
Study of developmental biology at German-speaking universities
Most universities have a chair for molecular developmental biology, some have dedicated institutes for embryology, such as the universities of Freiburg, Göttingen, or the LMU-Munich. or for plant embryology, for example at the University of Mainz. The LMU Munich states: "Embryology deals with all developmental processes from gametogenesis to embryogenesis and fetogenesis to birth, as well as the morphological aspects of the sexual cycle and pregnancy. Embryology thus provides essential basics for the important field of reproductive biology. " The University of Vienna offers the lectures Introduction to the Development and Comparative Developmental Biology of Vertebrates in the Biology Bachelor's degree. In addition to other universities, the universities of Vienna and Freiburg offer a master’s degree in genetics and developmental biology .
- Lewis Wolpert : Principles of Development: The original with translation aids. (= Easy Reading Information Series ). 3. Edition. Spectrum Academic Publishing House, 2007, ISBN 978-3-8274-1856-2 .
- Lewis Wolpert: Principles of Development. 4th edition. Oxford Univ. Press, 2011, ISBN 978-0-19-955428-7 . (English)
- Werner A. Müller, Monika Hassel: Developmental and reproductive biology of humans and animals. 5th, completely revised edition. Springer-Verlag , Berlin / Heidelberg / New York 2012, ISBN 978-3-642-28382-6 .
- Christiane Nüsslein-Volhard : The becoming of life. How genes control development. dtv, Munich 2006, ISBN 3-423-34320-6 .
- Scott F. Gilbert: Developmental Biology. 10th edition. Sinauer Associates, Sunderland 2013, ISBN 978-0-87893-978-7 .
- Michael Kühl, Susanne Gessert: Developmental Biology . 1st edition. UTB basics paperback, 2010, ISBN 978-3-8252-3331-0 .
- Shirley J. Wright: A Photographic Atlas of Developmental Biology. (Loose leaf collection). 2005, ISBN 0-89582-629-1 .
- Max Planck Institute for Developmental Biology
- Society for Developmental Biology (GfE)
- Developmental Biology and Bioinformatics (English)
- Compilation of some online resources on developmental biology
- Developmental biology clearly arranged for pupils and students
- UNSW Embryology
- Morphogenesis and Embryogenesis
- Chicken Development (Video)
- Frog development (video)
- Zebrafish Somite Development (Video)
- Eric Wieschaus: Patterning Development in the Embryo (Video)
- Lots of videos and animations on YouTube about cleavage and gastrulation.
- Ernst Haeckel: General Morphology of Organisms. Berlin 1866.
- Werner A. Müller, Monika Hassel: Developmental and reproductive biology of humans and animals. 3rd, completely revised Edition. Springer, 2003.
- Neil A. Campbell, Jane B. Reece: Biology. 6., revised. Edition. Pearson Studies, 2006.
- Michael Kühl, Susanne Gessert: Developmental Biology . UTB basics, 2010.
- Alan Turing: The chemical basis of morphogenesis. (PDF; 1.2 MB). In: Phil. Trans. R. Soc. London B 237, 1952, pp. 37-72. (Original article)
- H. Meinhard , A. Gierer : Application of a theory of biological pattern formation based on lateral inhibition. In: J. Cell Sci. 15, 1974, pp. 321-346.
- Mark C. Kirschner , John C. Gerhart: The solution to Darwin's dilemma - How evolution creates complex life. Rowohlt, 2007, ISBN 978-3-499-62237-3 . (Orig .: The Plausibility of Life, 2005)
- UNSW Embryology: Mouse Timeline Detailed
- Christiane Nüsslein-Volhard : The becoming of life. How genes control development. Munich 2006.
- University of Freiburg: Molecular Embryology ( Memento of the original dated November 3, 2014 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.
- University of Göttingen: Embryology
- Chair of Anatomy, Histology and Embryology ( Memento from June 26, 2015 in the Internet Archive )
- University of Mainz: Plant Embryrology
- Embryology LMU Munich
- University of Vienna: Master's degree: Genetics and Developmental Biology ( Memento from November 3, 2014 in the Internet Archive )
- University of Freiburg: Master's degree: Genetics and Developmental Biology